Diltiazem enhances the protective activity of oxcarbazepine against maximal electroshock-induced seizures in mice
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Department of Pathophysiology, Medical University, Lublin, Poland
Department of Cardiology, Medical University, Lublin, Poland
Department of Internal Medicine, Medical University, Lublin, Poland
Department of Obstetrics and Perinatology, Medical University, Lublin, Poland
Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland
JPCCR 2008;2(2):147–152
The aim of the study was to assess the eff ect of diltiazem (a calcium channel antagonist) on the anticonvulsant activity and acute adverse-eff ect potential of oxcarbazepine (a second-generation antiepileptic drug) in the maximal electroshock seizure (MES) model and chimney test in mice. Total brain concentrations of oxcarbazepine were measured with high pressure liquid chromatography (HPLC) to ascertain any pharmacokinetic contribution to the pharmacodynamic interaction between drugs. Results indicate that diltiazem (at a dose of 5 mg/kg, i.p.) signifi cantly enhanced the anticonvulsant activity of oxcarbazepine in the MES test in mice, by reducing the median eff ective dose (ED50 value) of oxcarbazepine from 14.25 to 9.87 mg/kg (P<0.01). In contrast, diltiazem at lower doses of 1.25 and 2.5 mg/kg had no signifi cant impact on the antiseizure action of oxcarbazepine in the MES test in mice. In the chimney test, diltiazem (up to 5 mg/kg, i.p.) did not signifi cantly aff ect the acute adverse eff ect potential of oxcarbazepine, and the median toxic dose (TD50 value) of the studied antiepileptic drug ranged from 74.16-62.91 mg/kg. Moreover, diltiazem (5 mg/kg) did not signifi cantly alter total brain oxcarbazepine concentrations as measured with HPLC. In conclusion, diltiazem ameliorates the pharmacological profi le of oxcarbazepine, when considering both the antiseizure and acute adverse eff ects of the antiepileptic drug in preclinical study on animals. The observed interaction between oxcarbazepine and diltiazem in the MES test was pharmacodynamic in nature; therefore, this favourable combination deserves more attention from a clinical point of view
Jarogniew J. Łuszczki   
Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
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